Todd A. Jusko

Blood lead concentrations < 10 microg/dL and child intelligence at 6 years of age.

Background Few studies provide data directly relevant to the question of whether blood lead concentrations < 10 μg/dL adversely affect children’s cognitive function. Objective We examined the association between blood lead concentrations assessed throughout early childhood and children’s IQ at 6 years of age. Methods Children were followed from 6 months to 6 years of age, with determination of blood lead concentrations at 6, 12, 18, and 24 months, and 3, 4, 5, and 6 years of age. At 6 years of age, intelligence was assessed in 194 children using the Wechsler Preschool and Primary Scale of Intelligence–Revised. We used general linear and semiparametic models to estimate and test the association between blood lead concentration and IQ. Results After adjustment for maternal IQ, HOME scale scores, and other potential confounding factors, lifetime average blood lead concentration (mean = 7.2 μg/dL; median = 6.2 μg/dL) was inversely associated with Full-Scale IQ (p = 0.006) and Performance IQ scores (p = 0.002). Compared with children who had lifetime average blood lead concentrations < 5 μg/dL, children with lifetime average concentrations between 5 and 9.9 μg/dL scored 4.9 points lower on Full-Scale IQ (91.3 vs. 86.4, p = 0.03). Nonlinear modeling of the peak blood lead concentration revealed an inverse association (p = 0.003) between peak blood lead levels and Full-Scale IQ down to 2.1 μg/dL, the lowest observed peak blood lead concentration in our study. Conclusions Evidence from this cohort indicates that children’s intellectual functioning at 6 years of age is impaired by blood lead concentrations well below 10 μg/dL, the Centers for Disease Control and Prevention definition of an elevated blood lead level.

Prevalence and sociodemographic correlates of antinuclear antibodies in the United States

OBJECTIVE To estimate the prevalence, types, and sociodemographic and biobehavioral correlates of antinuclear antibodies (ANAs) in the US. METHODS We conducted a cross-sectional analysis of 4,754 individuals from the National Health and Nutrition Examination Survey 1999-2004. ANAs were assessed by indirect immunofluorescence. In ANA-positive individuals, cellular staining patterns were determined, and specific autoantibody reactivities were assessed by immunoprecipitation. RESULTS The ANA prevalence in the US population of individuals ages 12 years and older was 13.8% (95% confidence interval [95% CI] 12.2-15.5%). ANA prevalence increased with age (P=0.01), and ANAs were more prevalent among females than males (17.8% versus 9.6%; P<0.001), with the female-to-male ratio peaking at 40-49 years of age. ANA prevalence was modestly higher in African Americans compared with whites (age-adjusted prevalence odds ratio [POR] 1.30, 95% CI 1.00-1.70). Remarkably, ANAs were less common in overweight and obese individuals (age-adjusted POR 0.74) than in persons of normal weight. No significant associations of ANA with education, family income, alcohol use, smoking history, serum levels of cotinine, or C-reactive protein were observed. In ANA-positive individuals, nuclear patterns were seen in 84.6%, cytoplasmic patterns were seen in 21.8%, and nucleolar patterns were seen in 6.1%; the most common specific autoantibodies were anti-Ro (3.9%) and anti-Su (2.4%). CONCLUSION These findings suggest that more than 32 million persons in the US have ANAs, and that the prevalence is higher among females, older individuals, African Americans, and those with a normal body weight. These data will serve as a useful baseline for future investigations of predictors and changes in ANA prevalence over time.

A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio

BackgroundPolychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals that persist in the environment and in human fatty tissue. PCBs are related to a class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro-dibenzodioxin), which has been implicated as a cause of altered sex ratio, especially in relation to paternal exposures.MethodsIn the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20°C. For this study, samples were thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex ratio, or sex ratio at birth, was evaluated as a function of maternal serum concentrations using log-binomial and logistic regression, controlling for hormonally active medications taken during pregnancy.ResultsThe relative risk of a male birth decreased by 33% comparing women at the 90th percentile of total PCBs with women at the 10th percentile (RR = 0.67; 95% CI, 0.48–0.94; p = 0.02), or by approximately 7% for each 1 μg/L increase in total PCB concentration. Although some congener-specific associations with sex ratio were only marginally statistically significant, all nine PCB congeners with < 30% of samples below the LOQ showed the same direction of association, an improbable finding under the null hypothesis.ConclusionMaternal exposure to PCBs may be detrimental to the success of male sperm or to the survival of male embryos. Findings could be due to contaminants, metabolites or PCBs themselves.

Reliability of triclosan measures in repeated urine samples from Norwegian pregnant women

Triclosan (TCS) is a synthetic antibacterial chemical that is used in personal care products and is measurable in urine. Urinary TCS has been associated with allergy in children in Norway and the United States. A reasonable degree of temporal reliability of TCS urinary concentrations has been reported among US children as well as for Puerto Rican pregnant women. We examined the reliability of TCS measures in urine among Norwegian pregnant women. TCS was measured in spot urine samples collected in gestational weeks 17, 23, and 29 from 45 women in The Norwegian Mother and Child Cohort Study (MoBa) enrolled in 2007 and 2008. Spearman’s rank correlation coefficient (rs) and intraclass correlation coefficient (ICC) statistics were calculated. Fifty-six percent of the 45 women had a least one sample with a value above the method limit of detection (2.3 μg/l). The correlation coefficients were 0.61 for TCS concentrations at 17 and 23 weeks and 0.49 for concentrations at 17 and 29 weeks. For the three time points, the ICC was 0.49. The reliability of TCS concentrations in repeated urine samples from pregnant Norwegian women was reasonably good, suggesting a single urine sample can adequately represent TCS exposure during pregnancy.

Maternal DDT Exposures in Relation to Fetal and 5-Year Growth

Background: Dichlorodiphenyltrichloroethane (DDT) is an organochlorine pesticide still used in areas of the world where malaria vector control is needed. Few studies have examined in utero exposures to DDT in relation to fetal and early childhood growth in populations with substantial exposure to DDT. Furthermore, only a portion of these studies have investigated in utero exposures and growth during childhood. Methods: To assess the role of in utero exposures to DDT on fetal and early childhood growth, we analyzed data from mothers and children who participated in the Child Health and Development Study (CHDS), a cohort study of 20,754 women and their pregnancies conducted in the San Francisco Bay area during the 1960s. We measured p,p′-DDE, o,p′-DDT, and p,p′-DDT concentrations from the stored sera of 399 women collected during pregnancy. Outcomes were measured at the childs birth and at 5 years of age. Results: Maternal p,p′-DDE concentrations were considerable in this study, averaging 6.9 micrograms per gram lipid. After covariate adjustment, a small increase in gestational age was observed with increases in p,p′-DDT and o,p′-DDT, but there was no association with p,p′-DDE. At 5 years of age, an increase from the 25th to the 75th percentile in p,p′-DDE was related to a 2-mm increase in head circumference (95% confidence interval = 0 to 4). Overall effect sizes were small and imprecise. Furthermore, there was little evidence of specificity for a given outcome or exposure at either age. Conclusions: At the concentrations studied in this sample, DDT compounds did not appear to impair fetal or 5-year growth.

A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age.

BACKGROUND Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. METHODS The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. RESULTS Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. CONCLUSIONS At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

Pre- and Postnatal Polychlorinated Biphenyl Concentrations and Longitudinal Measures of Thymus Volume in Infants

Background: Previously, we reported an association between higher maternal polychlorinated biphenyl (PCB) concentrations and smaller thymus volume in newborns in a birth cohort residing in eastern Slovakia. Objective: In the present report we address whether thymus volume at later ages is influenced by prenatal and early postnatal PCB exposure. Methods: At the time of delivery, 1,134 mother–infant pairs were enrolled. Maternal and 6- and 16-month infant blood samples were collected and analyzed for 15 PCB congeners. Thymus volume was measured in infants shortly after birth and at ages 6 and 16 months using ultrasonography. Results: Higher maternal PCB concentration was associated with reduced thymus volume at birth [a 0.21 SD reduction in thymus volume for an increase in total maternal PCB concentration from the 10th to the 90th percentile; 95% confidence interval (CI): –0.37, –0.05], whereas maternal PCB concentration was not predictive of 6- and 16-month thymus volume. Six-month infant PCB concentration was associated with a 0.40 SD decrease in 6-month thymus volume (95% CI: –0.76, –0.04). There was also some suggestion that thymus volume at 16 months was positively associated with concurrent infant PCB concentration. Conclusions: The potential adverse effects of in utero PCB exposure on thymic development may extend beyond the neonatal period. Results from this highly exposed cohort provide suggestive evidence that postnatal PCB concentrations may be influential, but a smaller set of 6-month PCB measurements limited statistical power at that time point. Implications regarding impaired immunologic maturation or long-term clinical implications remain to be determined.

The concentration of bisphenol A in urine is affected by specimen collection, a preservative, and handling

In urine specimens that were collected from pregnant women in a large cohort, 24% contained more than 10 ng/ml of total bisphenol A (BPA), suggesting external contamination. Therefore, we conducted an investigation of the source(s) of extraneous BPA in the specimens. We found that under the conditions used to collect urine specimens in the epidemiologic study, contamination with BPA occurred, and by two separate mechanisms.

Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants

Animal data indicate that developmental tetrachlorodibenzo-p-dioxin exposure alters immune function; however, the potential immunotoxicity of dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) in the developing infant is an understudied area. The aim of the current study is to examine the association between maternal and early postnatal PCB concentrations in relation to total infant serum immunoglobulin concentrations determined at 6-months-of-age. We selected 384 mother-infant pairs participating in a birth cohort study in Eastern Slovakia. PCB concentrations of several congeners were determined in maternal and cord serum samples and in infant serum samples collected at 6-months-of-age using gas chromatography with electron capture detection. Total immunoglobulin (Ig) G, A, and M concentrations were determined by nephelometry, and IgE concentrations were determined by enzyme-linked immunoassay. Linear regression models with adjustment for potential confounding factors were used to estimate the associations between maternal, cord, and 6-month infant PCB concentrations and total serum immunoglobulins. The median maternal serum concentration of PCB-153 was 140 ng/g lipid, ≈10-fold higher than concentrations in childbearing-age women in the United States during the same period. Maternal, cord, or 6-month infant PCB concentrations were not associated with total serum immunoglobulin levels at 6 months, regardless of the timing of PCB exposure, PCB congener, or specific immunoglobulin. In this population, which has high PCB concentrations relative to most populations in the world today, we did not observe any association between maternal and early postnatal PCB concentrations and total immunoglobulin measures of IgG, IgA, IgM, or IgE.

Reliability of concentrations of organophosphate pesticide metabolites in serial urine specimens from pregnancy in the Generation R Study

The widespread use of organophosphate (OP) pesticides has resulted in ubiquitous exposure in humans, primarily through their diet. Exposure to OP pesticides may have adverse health effects, including neurobehavioral deficits in children. The optimal design of new studies requires data on the reliability of urinary measures of exposure. In the present study, urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined in 120 pregnant women participating in the Generation R Study in Rotterdam. Intra-class correlation coefficients (ICCs) across serial urine specimens taken at <18, 18–25, and >25 weeks of pregnancy were determined to assess reliability. Geometric mean total DAP metabolite concentrations were 229 (GSD 2.2), 240 (GSD 2.1), and 224 (GSD 2.2) nmol/g creatinine across the three periods of gestation. Metabolite concentrations from the serial urine specimens in general correlated moderately. The ICCs for the six DAP metabolites ranged from 0.14 to 0.38 (0.30 for total DAPs), indicating weak to moderate reliability. Although the DAP metabolite levels observed in this study are slightly higher and slightly more correlated than in previous studies, the low to moderate reliability indicates a high degree of within-person variability, which presents challenges for designing well-powered epidemiological studies.